1. Field of the Invention
This invention relates generally to chronically implanted medical electrical leads and, in particular, to cardiac pacing leads which feature a drug which is no more than sparingly soluble in water applied to the electrode surface, e.g. beclomethasone dipropionate anhydrous.
2. Description of the Prior Art
Electrical stimulation of body tissue and organs is often used as a method of treating various pathological conditions. Such stimulation generally entails making an electrical contact between body tissue and an electrical pulse generator through use of one or more stimulation leads. Various lead structures and various techniques for implanting these lead structures into body tissue and particularly the heart have been developed.
For example, a transvenous endocardial lead establishes electrical contact between an electrical pulse generator and heart through placement of a lead in the venous system. Specifically, a transvenous endocardial lead is passed through a vein, with the assistance of a fluoroscope, into the heart where it may be held in contact with the endocardium by the trabeculae of the heart chamber, such as the ventricle. The safety, efficacy and longevity of an electrical pulse generator depends, in part, on the performance of its pacing lead(s).
During the past thirty years, there has been extensive research and development expended to optimize the performance of pacing leads and their reliability. In the early days of cardiac pacing, very high geometric surface area electrodes were employed with bulky and short-lived pacemaker pulse generators. Early investigators, such as Dr. Victor Parsonnet, advanced designs of pacing electrodes for achievement of low polarization and low thresholds while presenting a relatively small effective surface area for the delivery of a stimulating impulse in designs known as differential current density (DCD) of the type shown in U.S. Pat. No. 3,476,116. The DCD electrode (like all pacing electrodes of that time) suffered excessive chronic tissue inflammation and instability and was not pursued commercially.
Subsequent researchers, including Dr. Werner Irnich, explored in considerable detail the electrode-tissue interface and sought to arrive at an optimum exposed electrode surface area for both stimulation thresholds and sensing. See, for example Dr. Irnich, "Considerations in Electrode Design For Permanent Pacing" published in Cardiac Pacing; Proceedings of the Fourth International Symposium of Cardiac Pacing (H. J. Thalen, Ed.) 1973, pages 268-274.
Dr. Seymour Furman also studied the relationship of electrode size and efficiency for cardiac stimulation and presented a ball-tip/exposed spaced coil electrode and a small hemispheric electrode in his article entitled "Decreasing Electrode Size and Increasing Efficiency of Cardiac Stimulation" in Journal of Surgical Research, Volume 11 Number 3, Mar., 1971, pages 105-110. Dr. Furman concluded the practical lower limit of electrode surface area was in the range of 8 sq. mm, observing that impedance increased as an inverse function of the surface area.
Electrodes of many shapes including cylindrical, ball-tip, corkscrew, ring tip and open cage or "bird cage" configurations were pursued with exposed electrode surface areas tending toward 8 sq. mm in the mid 1970's.
More recently, various investigators have emphasized materials and their relationship to the considerations involved in optimizing electrode design. For example, the Medtronic U.S. Pat. No. 4,502,492 discloses a low polarization, low threshold electrode design of the early to mid 1980's which was commercialized as the "Target Tip".RTM. pacing leads in numerous models including Models 4011, 4012, 4511 and 4512. The tip electrode of the Target Tip lead was generally hemispherical and provided with circular grooves. The electrode was fabricated of a platinum alloy, coated over its external surface with a plating of platinum black. The combination of the relatively low electrode surface area and platinum black contributed to state-of-the-art thresholds in that time period. Other manufacturers marketed porous platinum mesh (Cardiac Pacemakers, Inc.), totally porous sintered (Cordis Corporation), glassy and vitreous carbons (Siemens), and laser drilled metal (Telectronics Ppty. Ltd.) electrodes in that same time period.
A considerable breakthrough in the development of low threshold electrode technology occurred with the invention of the steroid eluting porous pacing electrode of Stokes U.S. Pat. No. 4,506,680 and related Medtronic U.S. Pat. Nos. 4,577,642, 4,606,118 and 4,711,281, all incorporated herein by reference. The electrode disclosed in the '680 patent was constructed of porous, sintered platinum or titanium, although carbon and ceramic compositions were mentioned. Within the electrode, a plug of silicone rubber impregnated with the sodium salt of dexamethasone phosphate or a water soluble form of other glucocorticosteroids was placed in a chamber. The silicone rubber plug allowed the release of the steroid through the interstitial gaps in the porous sintered metal electrode to reach into the tissue and prevent or reduce inflammation, irritability and subsequent excess fibrosis of the tissue adjacent to the electrode itself.
In particular, the steroid is believed to act upon and inhibit the inflammatory response of the body. The presence of the electrode, an object foreign to the body, activates macrophages. This occurs approximately three days after implant. Once activated the macrophages attach themselves to the surface of the electrode and form multi-nucleated giant cells. These cells, in turn, secrete various substances, such a hydrogen peroxide as well as various enzymes, in an effort to dissolve the foreign object. Such substances, while intending to dissolve the foreign object, also inflict damage to the surrounding tissue. When the surrounding tissue is the myocardium, these substance cause necrosis. These areas of necrosis, in turn, cause the electrical characteristics of the electrode tissue interface to degrade. Consequently pacing thresholds rise. Even after the microscopic areas of tissue die the inflammatory response continues and approximately seven days after implant the multi-nucleated giant cells cause fibroblasts to begin laying down collagen to replace the necrosed myocardium. This continues until completed and the electrode is encapsulated by a thick layer of fibrotic tissue, approximately twenty-eight days after implant. Typically the inflammatory response ends at this time.
Steroid, it is believed, inhibits the inflammatory response by inhibiting the activation of the macrophages. Because they do not form multi-nucleated giant cells, the subsequent release of substances to dissolve the object and which also destroy the surrounding tissue is prevented. Thus the necrosis of any tissue by the inflammatory response is minimized as well as the formation of the fibrotic capsule. Minimizing each of these reactions also minimizes the concomitant deterioration of the electrical characteristics of the electrode-tissue interface.
Thus, the incorporation of steroid elution permitted pacing leads to have a source impedance substantially lower as compared to leads featuring similarly sized solid electrodes. Leads which elute steroid also presented significantly lower peak and chronic pacing thresholds than similarly sized solid or porous electrodes.
One example of a lead which eluted steroid meeting widespread commercial success is the Medtronic Model 5534 CAPSURE Z.TM. lead. In particular this lead features an electrode with an exposed geometric surface area in the range of 0.1-4.0 sq. mm , preferably between 0.6 and 3.0 sq. mm, with about 1.0 sq. mm providing optimum performance. The lead had a pacing impedance of 1400+/-260 ohms and a source impedance of about 1650+/-410 ohms in both chambers of the heart. The electrode was hemispherical as exposed to the tissue and had a diameter of approximately 1 millimeter. The electrode was further fabricated of platinized porous platinum (or other porous electrode material) and required an annular shaped monolithic controlled release device (MCRD) loaded with an anti-inflammatory agent soluble with water which would then elute out of the lead and into the surrounding tissue, e.g., the steroid dexamethasone sodium phosphate. This water soluble steroid also was deposited within the pores of the porous platinum electrode.
Incorporating steroid so that it will elute from a lead, however, dramatically increased the relative complexity of lead construction , especially as compared to past, non-steroid eluting leads. For example, leads which elute steroid typically require an MCRD to contain the steroid and to thereafter slowly leach out the water soluble steroid into the surrounding tissue. Typically MCRDs were constructed from silicone rubber. Steroid eluting leads also required an area near the electrode in which to house the MCRD, as well as a high degree of dimensional control over the electrode in order to ensure proper steroid elution. Moreover, because steroids which elute within the body, such as the sodium salt of dexamethasone phosphate, often degrade at high temperatures, thermal processing during the production of a steroid eluting lead was not allowed once the MCRD was installed. Setting aside a volume near the electrode tip to house the MCRD, however, also tended to increase lead body stiffness in that area.